EFFECT OF INTRAVENOUS CORTICOSTEROIDS ON DEATH WITHIN 14 DAYS IN 10,008 ADULTS WITH CLINICALLY SIGNIFICANT HEAD INJURY (MRC CRASH TRIAL):RANDOMISED PLACEBO-

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Presentation on theme: "EFFECT OF INTRAVENOUS CORTICOSTEROIDS ON DEATH WITHIN 14 DAYS IN 10,008 ADULTS WITH CLINICALLY SIGNIFICANT HEAD INJURY (MRC CRASH TRIAL):RANDOMISED PLACEBO-"— Presentation transcript:

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Summary Cortical steroids have been used to treat head injuries for more than 30 years.In 1997,findings after systematic review suggested that these drugs reduce the risk of death by 1-2%.The CRASH trial- a muliticentre international collaboration aimed to confirm or refute such an effect by recruiting 20,000 patients.In May,2004, the data monitoring committee disclosed the unmasked results to the steering committee,which stopped recruitment.

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Patients and methods Adults 16 yrs and above who presented within 8 hrs of injury and were noted in hospital to be having GCS of 14 and less.These were recruited if the treating doctor was uncertain whether or not to use steroids-(UNCERTANITY PRINCIPLE)

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Procedures Patients randomised in one of two ways. 1.reliable telephone access 2.Local pack system We randomly allocated patients to 48 h infusion of either methylprednisolone or placebo.Loading dose 2g over 1 h in 100mls of infusion.Maintenance dose 0.4g/h for 48h at rate of 20ml/h. Primary outcome measures were death from any cause within 2 weeks of injury and death or disability at 6 months.

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Statistical analysis Estimated risk of death allocated to placebo –15%. 2% survival difference would be clinically important so the trial size had to be large enough to detect a difference of this size.A trial of 20,000 patients would have a good chance of showing a 2% survival difference at convincing levels of significance ie >90% power to achieve p<0.01 Precision-95%CI for overall risk and 99%CI for subgroup results Homogenicity in treatment effects assessed within subgroups by X2 test at 5% significance level.

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Adherence to treatment-9,848(98%) 9,748(99%)received full loading dose. Mortality data obtained for 9,964 patients,4,985- CS M-1.052(21%) in 2wks, 4,979-P M- 893(18%) RR of death from all causes in 2wks in CS group with placebo 1.18 RR of death at 2wks didn’t differ by injury severity (p=0.22) or time since injury(p=0.05) Baseline characteristics-cont